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R Anwyl

Publications and source records attributed to R Anwyl.

At least 73 records · Page 4Linked to original sources
PubMed1994

5-HT1A receptor-mediated inhibition in the hippocampus of the alert rat--effects of repeated gepirone treatment.

The effects of acute and repeated treatment with the 5-HT1A receptor ligand gepirone on hippocampal excitatory synaptic transmission were investigated. Recordings of the electrically evoked field population excitatory postsynaptic potentials (e.p.s.p.s) were made in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert male Wistar rats. Acute injection of gepirone reduced the e.p.s.p. amplitude in a transient dose-dependent (0.5-10 mg/kg, i.p.) manner. This effect was blocked by the 5-HT1A receptor antagonist MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl methylaminoethys]-8- azaspiro[4,5]decane-7,9-dione methyl sulphonate, 2 mg/kg, i.p.). Gepirone (1 mg/kg per day, i.p.) administered for 7 days produced a gradual reduction in the daily pre-injection baseline e.p.s.p. amplitude coupled with a concomitant reduction of the acute response to the drug. The chronic baseline reduction was transiently reversed by the 5-HT1A receptor antagonist spiroxatrine and complete recovery to pretreatment levels was observed 48 h after the last gepirone dose. The data indicate that with repeated administration, a prolongation and enhancement of the 5-HT1A receptor-mediated reduction in the e.p.s.p. by gepirone occurs. This delayed effect may contribute to the slow onset of therapeutic action of gepirone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Long-lasting enhancement of NMDA receptor-mediated synaptic transmission by metabotropic glutamate receptor activation.

Synaptic transmission mediated by the N-methyl-D-aspartate (NMDA) glutamate receptor plays a key role in a range of plastic processes in the nervous system. These include long-term potentiation of synaptic transmission mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor, neuronal development, excitotoxicity and certain learning tasks. Recently, long-term potentiation of NMDA receptor-mediated synaptic transmission was found to occur following high-frequency (tetanic) stimulation via an unknown mechanism. We show here that activation of metabotropic glutamate (mGlu) receptors by neurally released transmitter underlies this type of long-term potentiation. The whole-cell patch-clamp technique in the 'thick' slice of the rat dentate gyrus was used to measure NMDA receptor-mediated excitatory postsynaptic currents. We have found that mGlu receptor activation by a selective agonist produced a long-lasting enhancement which was mutually exclusive with long-term potentiation of these NMDA currents. Moreover, both forms of potentiation were greatly reduced by the mGlu receptor antagonists L-2-amino-3-phosphonopropionate and (R,S)-alpha-methyl-4-carboxyphenylglycine.

Animals↗
PubMed1994

Adaptive changes in 5-HT1A receptor-mediated hippocampal inhibition in the alert rat produced by repeated 8-OH-DPAT treatment.

1. The effect of acute and repeated treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor ligand, on excitatory amino acid-mediated synaptic transmission was examined in the stratum radiatum CA1 region of the dorsal hippocampus of alert, gently restrained, rats. 2. Acute administration of 8-OH-DPAT transiently reduced the amplitude of the field excitatory postsynaptic potential (e.p.s.p.) in a dose-dependent (25-75 micrograms kg-1, i.p.) manner. This effect was blocked by the postsynaptic 5-HT1A receptor antagonist, MDL 73005EF (2 and 4 mg kg-1, i.p.). 3. 8-OH-DPAT (25 micrograms kg-1, i.p.) administered daily for 7 days produced a gradual reduction in the 24 h pre-injection baseline field e.p.s.p. amplitude. The reduction reached its lowest level after 7-8 days and was transiently reversed by acute injection of MDL 73005EF (2 mg kg-1, i.p.) on day 8. The field e.p.s.p. baseline amplitude recovered fully 5-8 days after cessation of drug treatment. 4. 8-OH-DPAT (25 micrograms kg-1, i.p.) administered daily for 7 days produced a marked reduction in acute response to 8-OH-DPAT (25 and 50 micrograms kg-1, i.p.) which did not recover until between day 36 and day 80 of the study. 5. It was concluded that repeated treatment with 8-OH-DPAT produced adaptive changes which resulted in a reduction in the dynamic range of 5-HT1A receptor-mediated transmission in the hippocampus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Use-dependent effects of acute and chronic treatment with imipramine and buspirone on excitatory synaptic transmission in the rat hippocampus in vivo.

The effects of acute and long-term treatment with imipramine and buspirone on the responses of rat hippocampal neurones to low and high frequency electrical stimulation were compared. Whereas acute treatment with imipramine (10 mg/kg, i.p.) had no effect on synaptic responses to low frequency stimulation, chronic treatment for 14 days significantly reduced the amplitude of the field excitatory postsynaptic potential. Both acute and chronic imipramine treatment markedly reduced the amplitude of the nerve volley and excitatory postsynaptic potential evoked at high frequency stimulation rates in a use-dependent manner. Buspirone (0.5-3 mg/kg, i.p.) produced a significant reduction of the excitatory postsynaptic potential at high frequencies. This was enhanced after repeated administration of a dose of 0.5 mg/kg for 14 days. We previously reported a similar effect of buspirone at low frequency stimulation. Both compounds therefore share the ability to exert strong depressant effects on transmission in the hippocampus especially after chronic treatment.

Animals↗
PubMed1992

Serotoninergic depression of auditory evoked responses recorded in the rat hippocampus: effect of repeated buspirone treatment.

Auditory evoked middle latency responses recorded in the hippocampus (HAER), were monitored in alert, gently restrained rats with chronic indwelling electrodes and cannulae. Intrahippocampal (i.h.) injection of 5-hydroxytryptamine (5-HT, 10 micrograms) reduced the amplitude and increased the latency of the N28 and P55 peaks of the HAER. An early (P18) negative peak was unaffected. Buspirone (1 microgram, i.h. and 3 mg/kg, i.p.) had similar effects to those produced by i.h. 5-HT. RU 24969 (1 mg/kg, s.c.) also reduced the amplitude of the N28 peak of the HAER. Long-term treatment with buspirone for 14 days at a dose (0.5 mg/kg, i.p.) which when applied acutely did not produce any observable effect, caused an increase in the latency of both the N28 and P55 peaks. Direct i.h. injection of 5-HT into these chronically treated animals did not have any additional depressant effect on the HAER peaks. It is concluded that these serotoninergic agonists can modulate the later peaks of the HAER possibly via 5-HT1A receptors. In the case of buspirone there was evidence of an enhanced depressant effect following chronic treatment [corrected].

Animals↗
PubMed1991

Inhibition of an N-methyl-D-aspartate induced short-term potentiation in the rat hippocampal slice.

The effects of the phorbol ester 4 beta-phorbol-12,13 dibutyrate (PDBu) and the protein kinase (PK) inhibitors H-7 and sphingosine were investigated on the short-term potentiation (STP) of the population excitatory postsynaptic potential (EPSP) induced by perfusion of N-methyl-D-aspartate (NMDA) in the stratum radiatum of CA1 of the rat hippocampal slice. Bath perfusion of 130 microM NMDA for 10 s caused an initial depression of the population EPSP followed by a STP, which averaged 46% and lasted 16 min. PDBu (100 nM) perfused for 2 h completely inhibited the NMDA induced STP, suggesting that the stimulation of PKC inhibited an NMDA receptor activated process which induced the STP. The protein kinase inhibitors H-7 and sphingosine did not alter the NMDA induced STP.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

The effects of external calcium on the N-methyl-D-aspartate induced short-term potentiation in the rat hippocampal slice.

The effect of altered extracellular Ca concentration was studied on the N-methyl-D-aspartate (NMDA) induced short-term potentiation (STP) of the population excitatory post-synaptic potential recorded from the stratum radiatum of CA1 of the rat hippocampal slice. Perfusion of 130 microM of NMDA for 10 s in control media containing 2.0 mM extracellular Ca evoked an STP with a maximum amplitude of 46% and a duration of 16 min. Perfusion of media containing a reduced Ca concentration of 0.8 mM or 1.0 mM did not alter the amplitude or time course of the STP. However, raising the Ca concentration to 3.0 mM or 4.0 mM caused a significant reduction in the amplitude of the STP to 23% and 2% respectively. The abolition of the NMDA induced STP in 4 mM Ca could not have been produced by response saturation since an identical long-term potentiation (LTP) was produced in this high Ca media as in the control media. These studies show that the NMDA induced STP has a very different Ca dependency to LTP.

Animals↗
PubMed1991

The effects of trans-ACPD on long-term potentiation in the rat hippocampal slice.

Trans-ACPD, a metabotropic glutamate receptor agonist, enhanced both the short-term potentiation (STP) at 1 and 5 min, and long-term potentiation (LTP) at 20 min, following tetanic stimulation, of the population, excitatory postsynaptic potential (epsp) recorded from CA1 of the rat hippocampal slice. The enhancement of both STP and LTP also occurred in the presence of the protein kinase inhibitor sphingosine, indicating that the enhancement is most likely to occur through the inositol phosphate rather than the protein kinase limb following receptor activation and phosphoinositide hydrolysis. LTP of the low frequency population epsp was not induced by t-ACPD, even at 100 microM. The metabotropic glutamate receptor may have an important role in LTP induction or modulation.

Animals↗
PubMed1990

Actions of 5-HT1 ligands on excitatory synaptic transmission in the hippocampus of alert rats.

1. The effects of 5-hydroxytryptamine1 (5-HT1) ligands on excitatory synaptic transmission were examined in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert, gently restrained, rats. 2. 5-HT produced a dose-dependent reduction in the amplitude of the electrically evoked population excitatory postsynaptic potential (e.p.s.p.) when injected directly into the hippocampus via a cannula (dose producing 50% maximum inhibition, ED50 = 0.46 microgram). 3. Direct intrahippocampal (i.h.) application of buspirone (ED50 = 0.29 microgram), gepirone (1 microgram), ipsapirone (1 microgram), BMY 7378 (0.1 microgram) and 5-carboxamidotryptamine (5-CT, 0.02 microgram) mimicked the inhibitory effect of 5-HT. 4. Systemic injection of buspirone (ED50 = 0.88 mg kg-1, i.p.), BMY 7378 (0.01 mg kg-1, i.p.) and RU 24969 (1 mg kg-1, s.c.) also had an inhibitory effect on the amplitude of the e.p.s.p. 5. Injection of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 2 micrograms) and spiroxatrine (1 microgram) i.h. alone had no effect on the e.p.s.p. amplitude but prevented the inhibitory effect of 5-HT. 6. Systemic injection (i.p.) of methysergide (5 mg kg-1) and spiroxatrine (1 mg kg-1) antagonized the inhibitory effect of buspirone whereas pretreatment with ketanserin (1 mg kg-1), trifluoperazine (1 mg kg-1) and idazoxan (1 mg kg-1) had no effect on the response to buspirone. 7. It is concluded that hippocampal synaptic transmission is highly sensitive to the agonist and antagonist properties of 5-HT1 ligands in the alert rat.

Adrenergic alpha-Antagonists↗
PubMed1989

The role of N-methyl-D-aspartate receptors in the generation of short-term potentiation in the rat hippocampus.

The effects of stimulus intensity and the N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovalerate (AP5) were studied on the induction of short-term potentiation (STP) and long-term potentiation (LTP) in CA1 of the rat hippocampal slice. A tetanus of very weak intensity stimuli produced STP, and also LTP providing the stimuli were applied in the form of a series of high frequency trains rather than one continuous train. Increasing the intensity of the stimuli to just threshold for spike initiation produced larger amplitude STP and LTP. AP5 strongly inhibited the STP as well as the LTP produced by a series of high frequency trains, indicating a large component of this STP was generated by activation of NMDA receptors. A further residual component of STP in AP5, which was associated with a decrease in paired pulse facilitation, is probably generated by a presynaptic increase in the probability of transmitter release.

2-Amino-5-phosphonovalerate↗
PubMed1989

Serotonergic involvement in the inhibitory effects of repeated buspirone treatment on synaptic transmission in the hippocampus.

The effects of acute and long-term treatment with buspirone on synaptic transmission in the hippocampus were compared in alert rats with chronic indwelling electrodes and cannula. Buspirone produced a transient dose-dependent reduction in the amplitude of the excitatory postsynaptic potential (EPSP) when acutely injected either systemically (0.3-3.0 mg/kg i.p.) or directly into the hippocampus (0.1-1.0 microgram i.h.). Whereas acute application of 0.5 mg/kg i.p. produced a 20% reduction which reversed within 2 h, during long-term treatment with this relatively low dose there was a gradual reduction of the baseline EPSP amplitude which reached a maximum (40%) between days 7-14 and which did not reverse completely until 72 h after the last injection. Intrahippocampal injection of either buspirone or 5-hydroxytryptamine did not have any additional effect during the period of baseline reduction. The 5-HT1A receptor antagonist spiroxatrine (1 mg/kg i.p.) produced a transient reversal of the effect of chronic buspirone. It is concluded that the chronic inhibitory effect of buspirone is probably an extension of its acute action on 5-HT1A receptors in the hippocampus.

Animals↗
PubMed1989

Protein kinase C and long-term potentiation in the hippocampus.

A number of recent studies have implicated a role of the Ca2+-dependent protein kinase C in the generation of long-term potentiation in the hippocampus. Membrane protein kinase C activity was increased following a high frequency tetanus that produced long-term potentiation; and intracellular injection of protein kinase C caused enhancement of synaptic transmission identical to that occurring during long-term potentiation. Roger Anwyl describes studies using inhibitors and activators of protein kinase C which suggest that a late, nondecremental component of long-term potentiation is dependent on protein kinase C activation, although an early, short-lasting decremental component of long-term potentiation is probably independent of its activity.

Animals↗
PubMed1988

The role of calcium in short-term potentiation in the rat hippocampal slice.

Short-term potentiation of extracellular field excitatory postsynaptic potentials (EPSP's) was investigated in the stratum radiatum of CA1 of the rat hippocampal slice in vitro. A presynaptic tetanus consisting of a single train of stimuli at 250 Hz evoked short-term potentiation (STP), but not long-term potentiation (LTP) of small amplitude, just suprathreshold, EPSP's in a medium containing 2 mM Ca and 2 mM Mg. Increasing the number of stimuli in the tetanus enhanced the initial amplitude of the STP to a maximum of 40-70% with 30-40 stimuli, and enhanced the decay time constant of STP to a maximum of 60-80 s. Increasing the Ca influx by raising external Ca, lowering Mg or adding the agent 4-aminopyridine caused a large increase in the initial amplitude of STP but only a very slight increase in the decay time of STP. LTP was frequently evoked in high Ca/Mg ratios of 2.0 or 4.0, but not in 1.0 or 0.5.

Action Potentials↗
PubMed1988

The effects of external calcium on long-term potentiation in the rat hippocampal slice.

Extracellular excitatory postsynaptic potentials (EPSPs) were recorded from the stratum radiatum of CA1 of the rat hippocampal slice. The effect of altering the external Ca concentration was studied on the amplitude of the low frequency evoked EPSP preceding and following the production of long-term potentiation (LTP). The double logarithmic plot of the relationship between the EPSP amplitude and external Ca had a maximum slope of 2.1, implying Ca cooperativity in transmitter release. The production of LTP did not alter the slope. The amplitude of LTP was found to be highly dependent on the external Ca concentration, with LTP increasing from a 5% increase in the EPSP amplitude in 0.8 mM Ca, to a 65% increase in the EPSP amplitude in 2.0 mM Ca.

Animals↗